Left Ventricular Mass Index Research Articles

Assessing coronary artery stenosis exacerbated impact on left ventricular function and deformation in metabolic syndrome patients by 3.0 T cardiac magnetic resonance imaging

Abstract Background Metabolic syndrome (MetS) and coronary artery stenosis (CAS) independently increase the risk of cardiovascular events, while the impact of CAS on left ventricular (LV) function and deformation in MetS patients remains unclear. This study investigates how varying degrees of CAS exacerbate LV function and myocardial deformation in MetS patients. Methods One hundred thirty-one MetS patients who underwent CMR examinations were divided into two groups: the MetS(CAS−) group (n = 47) and the MetS(CAS+) group (n = 84). The MetS(CAS+) group was divided into MetS with non-obstructive CAS(NOCAS+) (n = 30) and MetS with obstructive CAS(OCAS+) group (n = 54). Additionally, 48 age- and sex-matched subjects were included as a control group. LV functional and deformation parameters were measured and compared among subgroups. The determinants of decreased LV global peak strains in all MetS patients were identified using linear regression. The receiver operating characteristic (ROC) curve and logistic regression model (LRM) evaluated the diagnostic accuracy of the degree of CAS for identifying impaired LV strain. Results Compared to MetS(CAS−), MetS(NOCAS+) showed a significantly increased LV mass index (p < 0.05). Global longitudinal peak strain was decreased gradually from MetS(CAS−) through MetS(NOCAS+) to MetS(OCAS+) (− 13.02 ± 2.32% vs. − 10.34 ± 4.05% vs. − 7.55 ± 4.48%, p < 0.05). MetS(OCAS+) groups showed significantly decreased LV global peak strain (GPS), PSSR and PDSR in radial and circumferential directions compared with MetS(NOCAS+) (all p < 0.05). The degree of CAS was independently associated with impaired global radial peak strain (GRPS) (β = − 0.289, p < 0.001) and global longitudinal peak strain (GLPS) (β = 0.254, p = 0.004) in MetS patients. The ROC analysis showed that the degree of CAS can predict impaired GRPS (AUC = 0.730) and impaired GLPS (AUC = 0.685). Conclusion Besides traditional biochemical indicators, incorporating CAS assessment and CMR assessment of the LV into routine evaluations ensures a more holistic approach to managing MetS patients. Timely intervention of CAS is crucial for improving cardiovascular outcomes in this high-risk population.

Correlation between indole-3-acetic acid and left ventricular hypertrophy in hemodialysis patients.

Among hemodialysis patients, left ventricular hypertrophy (LVH) is a prevalent cardiac abnormality. The uremic toxin indole-3-acetic acid (IAA) is elevated in uremia patients, but the connection between IAA and LVH in individuals undergoing hemodialysis remains uncertain. Hence, the objective of this research was to examine the correlation between blood IAA levels and LVH in individuals undergoing hemodialysis. In total, 205 individuals undergoing hemodialysis were chosen and categorized into two groups, with (143 patients) and without LVH (62 patients). Patient clinical data were collected, and serum creatinine, calcium, phosphorus, hemoglobin, and IAA levels were measured. Compared to the non-LVH group, the LVH group had higher IAA and serum phosphorus but lower hemoglobin. The serum IAA concentration was positively correlated with both left ventricular mass (LVM) and left ventricular mass index (LVMI) but negatively correlated with both left ventricular ejection fraction (LVEF) and the ratio of left ventricular transmitral early peak flow velocity to left ventricular transmitral late peak flow velocity (E/A). Logistic regression analysis indicated that increased IAA levels are a risk factor for LVH and are not influenced by other factors. In addition, we exposed primary neonatal cultured mouse cardiomyocytes to varying concentrations of IAA in a controlled environment. Cardiomyocyte hypertrophy was induced by IAA in a concentration-dependent manner. Serum IAA is correlated with alterations in both the function and structure of the left ventricle. The serum IAA concentration is an independent risk factor for LVH. IAA may be a novel biomarker of LVH in hemodialysis patients.

Cardiac remodeling in elite young Asian female soccer players

IntroductionAn athlete's heart (AH) varies depending on race, sex, age, and the type and intensity of training. Given that soccer is a common sport, evaluation of cardiac function in soccer players is important; however, few studies have analyzed adolescent soccer players. Therefore, this study, aimed to identify early changes in AH in soccer players by evaluating the echocardiographic findings of adolescent Asian female soccer players for whom existing data are scarce.MethodsWe evaluated 20 Korean female under-20 national soccer team players and 42 age-matched healthy females. Participants provided physical examination data such as height, weight, blood pressure, and pulse, along with echocardiographic results. On echocardiography, parameters related to the morphology of the left atrium (LA) and left ventricle (LV) and those related to the systolic and diastolic function of the LV were measured.ResultsThe athlete group had a lower blood pressure and pulse rate than the control group. Echocardiography indicated that both the LA volume index and LV volume in the athlete group were large by approximately 1.5 times compared with those in the control group. The LV wall thickness and mass index were also significantly large in the athlete group. For LV diastolic function, parameters indicating early diastolic filling were substantially higher in the athlete group than in the control group.ConclusionsAdolescent female soccer players exhibited differences in cardiac morphology and an enhanced diastolic function. Therefore, this study suggests that AH begins in adolescence, with changes in both morphology and function.

Left Ventricular Hypertrophy in Women With a History of Preeclampsia.

As a hypertensive disorder of pregnancy, preeclampsia is associated with increased cardiovascular morbidity and mortality later in life. Since early signs of myocardial affection could indicate a higher risk of future cardiovascular disease manifestations, we investigated whether women with prior preeclampsia have a higher prevalence of left ventricular hypertrophy compared with women from the general population and to what extent chronic hypertension affects any potential difference. In a cohort study, women aged 40 to 55 years with prior preeclampsia were compared with age- and parity-matched women from the general population. They underwent a research cardiac computed tomography, and the primary outcome was left ventricular hypertrophy, defined as a left ventricular mass index >30 g/m2.7. In 679 women with prior preeclampsia and 672 controls (median age, 47 years), we found a higher prevalence of left ventricular hypertrophy (14.0% versus 6.4%) in the preeclampsia group with an odds ratio of 1.62, 95% CI (1.07-2.46), P=0.024, median of 15 years (range, 0-28) after pregnancy, after adjustment for cardiovascular risk factors, including chronic hypertension. Left ventricular hypertrophy was more frequent among women with preeclampsia with (26.2% versus 15.6%) and without (5.5% versus 2.4%) chronic hypertension, and a mediation analysis showed that chronic hypertension explained 22% of the association between preeclampsia and left ventricular hypertrophy. Women with prior preeclampsia had a 2-fold higher prevalence of left ventricular hypertrophy compared with women from the general population, and preeclampsia was independently associated with left ventricular hypertrophy, regardless of the presence of cardiovascular risk factors, including chronic hypertension. URL: https://www.clinicalTrials.gov; Unique identifier: NCT03949829.

Electrocardiographic strain and relationship with LV remodelling and clinical outcomes in patients with aortic stenosis undergoing transcatheter aortic valve implantation.

Left ventricular (LV) remodelling and fibrosis is known to occur in patients with aortic stenosis (AS) and is linked to post-intervention outcomes. These myocardial changes may be detected upon the routine 12-lead electrocardiogram by the presence of a LV strain pattern (LVS-ECG). Although LVS-ECG has been related to excessive cardiovascular morbidity and mortality in multiple patient populations, there is currently a dearth of data upon its impact in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the current study was to investigate the prevalence, predictors and prognostic value of LVS-ECG. Between 2012 and 2019, 640 consecutive patients underwent TAVI at Haukeland University Hospital, Bergen. Of these, 600 patients with severe AS were included in the TAVI-NOR study. Patients with known bundle branch block (n=85) or permanent pacing (n=25) were excluded, leaving 490 patients (mean age 81±6years, 52% females) eligible for the analyses. LVS-ECG was defined as down-sloping, convex ST-segment depression with asymmetric T-wave inversion in V5 or V6. LVS-ECG was present in 25.7% patients. Higher levels of NT-proBNP (OR 1.96; 95% CI:1.08-3.55, p=0.028), LVEF<50% (OR 3.14; 95% CI:1.61-6.13, p=0.001), increase in LV mass index per SD (32g/m2) (OR 1.37; 95 CI:1.06-1.76, p=0.014), and the presence of LV hypertrophy on ECG (OR 3.23; 95% CI:1.97-5.32, p<0.001) were independent predictors of LVS-ECG in the multivariable-adjusted analysis. Although all-cause mortality was significantly higher in patients with LVS-ECG compared to those without (54.8% vs 44.2%, p=0.041), the presence of LVS-ECG did not predict all-cause mortality during a median follow-up of 64±24 months (HR 1.05; 95% CI:0.79-1.39, p=0.742). Patients with LVEF <50% and concomitant LVS-ECG had a worse prognosis than those with LVEF >50% and no LVS-ECG (p<0.001). LVS-ECG may represent a simple marker of structural and functional LV remodelling that signals a propensity to excess mortality during long-term follow-up after TAVI, as it is strongly associated with other prognosticators such as reduced LVEF and increased levels of NT-proBNP.

Abstract 4135861: Lipoprotein(a) and Its Impact on Left Ventricular Remodeling Over a Decade: The Multi-Ethnic Study of Atherosclerosis

Background: Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown. Objectives: This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease. Methods: 2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[&lt;7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[&gt;38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling ( Table ). Results: Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m 2 ; P = 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m 2 ; P = 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %; P = 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors ( Table ). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m 2 ; P = 0.01), LV indexed mass (β 1.17 g/m 2 ; P = 0.02) and a decrease in LV ejection fraction (β -1.01 %; P = 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 ( Table - Model 3), and baseline coronary artery calcium score and interim myocardial infarction ( Table - Model 4). Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Abstract 4122389: Accumulation of Epicardial Adipose Tissue as a Marker of Diastolic Dysfunction in Patients With Preserved Left Ventricular Ejection Fraction Undergoing Coronary Computed Tomography Angiograph

Background: Left ventricular diastolic dysfunction (LVDD) plays a major role in the pathophysiology of progression to heart failure with preserved left ventricular (LV) ejection fraction (EF). Although epicardial adipose tissue (EAT) is attracting attention for the underlying pathophysiology, whether increased EAT and coronary plaque burden are associated with LVDD is unclear in patients with chronic coronary artery disease (CAD) and preserved LVEF. Aims: To investigate the association between LVDD and EAT accumulation in chronic CAD patients with preserved LVEF. Methods: We included three hundred fourteen chronic CAD and preserved LVEF patients without history of heart failure (mean age: 66±13 years; 48% female). Thoracic tissue doppler echocardiography (TTDE) analysis included LVDD parameters, including left atrial volume index (LAVI), e’, E/e’ and tricuspid regurgitation (TR) velocity. LVDD was defined according to the American Society of Echocardiography guidelines. Coronary computed tomographic angiography (CCTA) analysis included EAT volume index (EAVi), coronary artery calcium score (CACS), and coronary plaque volume (%PV). Patients were divided into three groups according to EAVi: Group A as normal (&lt;68.1 ml/m 2 , n=127), group B as low (68.1-89.4 ml/m 2 , n=95), and group C as high EATVi (&gt;89.4 ml/m 2 , n=92). Multivariable logistic regression analysis was performed to investigate the association between the clinical parameters, TTDE and CCTA findings, and the presence of LVDD. Results: Compared with Group A, group C was older and more frequently suffered from renal dysfunction. Among the three groups, we observed significant differences in LV mass index, e’, E/e’, and CACS. The EAVi correlated with each LVDD diagnostic component, including e’, E/e’, left atrial volume index (all p&lt;0.05), except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; 95% CI, 1.06-1.20; p&lt;0.001] and EAVi (OR, 1.03; 95%CI, 1.01-1.04; p&lt;0.05) were independently associated with LVDD, even after adjusting for LV mass index (OR, 1.1; p &lt; 0.05). There was no independent association of CACS or %PV with LVDD (Table). Conclusion: This study demonstrates that accumulation of EAT and LV mass index but not plaque volume were independent predictors of LVDD in chronic CAD patients with preserved LVEF. Further study is needed to investigate whether EAT predicts the development to heart failure in this population.

Abstract 4141472: Birthweight is Associated with Left Ventricular Mass Index in Childhood

Introduction/Background: Increased left ventricular mass (LVM) is a risk factor for adult CV disease and is associated with cardiac development in utero. Associations of birthweight with LVM have been demonstrated in young children and adolescence, however, the association between birth weight and LVM in mid-childhood is not well described. Research Questions/Hypothesis: Utilizing an existing longitudinal data set of healthy children, we aimed to determine the association of birthweight to increased LVM at 6-8 years of age. Methods/Approach: A longitudinal cohort of 372 term-born children was enrolled at age 3 and followed until age 6-8 years. Anthropometrics, echocardiography, and maternal recall of birth weight were collected. LVM from echocardiography was indexed to height 2.7 . Multiple linear regression analysis was performed to assess the association of birthweight with LVM index at 6-8 years of age, adjusting for race, sex, body mass index (BMI) z-score, and systolic blood pressure (SBP) percentile collected at the time of echocardiography. Results: 303 children were included in the analysis (21.5% Black and 88.5% White, mean age 7.4 ± 0.3 years at the time of echocardiography, mean birthweight 3.4 ± 0.6 kg, mean SBP percentile 42.7 ± 21.6 percentile). Greater birthweight significantly contributed to greater LVM index (1.2 ± 0.6, p = 0.03), along with Black race (1.9 ± 0.8, p = 0.02) and greater current BMI z-score (2.1 ± 0.3, p &lt; 0.01). Sex and SBP percentile were included in the model but were not significantly related to LVM index (p = 0.23 and 0.51 respectively) in this analysis. Conclusions: Greater birthweight is significantly associated with greater left ventricular mass in childhood, independent of BMI z-score at the time of echocardiography. This suggests a critical period in fetal cardiac development that affects cardiac structure in mid-childhood.

Abstract 4120577: Discrimination of Fabry Disease and Cardiac Amyloidosis Using Cardiac MRI and Echocardiography: A Comprehensive Analysis

Background: Discriminating Fabry disease from cardiac amyloidosis based on conventional imaging techniques can be challenging due to overlapping features. We aimed to investigate the discriminatory ability of cardiac MRI (CMR) and echocardiography imaging, to differentiate between these conditions. Methods: Cardiac MRI and echocardiography with SR imaging were performed on patients with suspected Fabry disease (n=39) or cardiac amyloidosis (n=79). Various imaging parameters, including late gadolinium enhancement (LGE) patterns and T1 mapping values derived from CMR, E/e’ and global longitudinal strain (GLS) were analyzed. Discrimination scores were calculated using multivariate analysis, with sensitivity and specificity determined for selected parameters. Results: In Fabry patients, LGE patterns predominantly exhibited a subendocardial distribution (66%), whereas amyloidosis patients showed transmural LGE (93%). LV mass index and T1 mapping values were higher (150±20 vs. 90±15 g/m 2 , 1208±104 vs. 822± 210ms both p p&lt;0.001) in cardiac amyloidosis compared to Fabry disease. Echocardiographic parameters demonstrated significantly reduced GLS (-12±2 vs -18±3%, p&lt;0.001), larger LA size (50 ± 5 mm vs. 40 ± 5 mm, p&lt;0.001) and higher E/e' ratio (15 ± 3 vs. 8 ± 2, p&lt;0.001) in cardiac amyloidosis compared to Fabry disease. Multivariate analysis identified LGE patterns and GLS as significant discriminators, and combining both parameters can discriminate Fabry and Amyloidosis with a sensitivity of 80.0%, specificity of 90.0%, and predictive accuracy of 85.0%. Incorporating LA size, LV mass index and E/e’ further improve the predictive accuracy to 92.0%. Conclusions: Cardiac MRI and echocardiography demonstrate promising discriminatory ability in distinguishing Fabry disease from cardiac amyloidosis. GLS emerges as a valuable parameter, reflecting myocardial function and aiding in accurate diagnosis. Integration of these imaging modalities into clinical practice could enhance diagnostic accuracy and guide appropriate management strategies.

Abstract 4146311: Cardiac Thickening, Cell Free DNA, and Rejection in the 2 nd Porcine Cardiac Xenograft

Introduction/Background: A 58-year-old man with inotrope dependent heart failure was declined for allotransplant and MCS at multiple centers and was transplanted with a 10 gene-edited porcine cardiac xenograft under FDA expanded access Investigational New Drug (eIND) approval. After requiring perioperative transfusions, by post operative day (POD) 13, endomyocardial biopsy revealed antibody and complement deposition without damage or cellular infiltrate. Hemodynamic decompensation on POD 29 prompted biopsy revealing antibody mediated rejection (AMR). The patient required ECMO support POD31 and chose comfort care POD 40. Research Questions/Hypothesis: The cardiac xenograft doubled in mass from implant to autopsy. Donor derived cell free DNA (cfDNA) correlated temporally with the rejection findings. These processes are hypothesized to correlate. Approach: Routine TTE measurements of diastolic LV posterior wall dimension (LVPWd), intraventricular septal dimension (IVSd), LV mass, and LV mass index were taken. Donor derived cfDNA was measured weekly and PRN (Care Dx Inc., Brisbane, CA). Pearson correlation coefficient analysis was conducted in GraphPad Prism 10 (Dotmatics, Boston, MA). Results/Data: POD 26 TTE measurements indicated thickening graft. POD 30 cfDNA began elevating. cfDNA correlated moderately with LVPWd (r = 0.43, p=0.4) and IVSd (r= 0.5, p=0.31) less so with LV mass (r= 0.28, p=0.59) and LV mass index (r=0.34, p=0.51) Conclusions: Xenograft cardiac thickening measured on TTE preceded elevation in cfDNA. Both were moderately correlated and temporally corresponded to biopsy diagnosed AMR and ultimate graft failure. Future xenograft surveillance will likely benefit from multimodal approach.

Abstract 4126731: Cumulative Cardiovascular Health in Young Adulthood and Systemic Target Organ Damage: The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Introduction: Cardiovascular health (CVH) in young adulthood (YA) is strongly associated with subclinical and clinical outcomes in later life. Longitudinal patterns of CVH exposure through YA (e.g., cumulative CVH exposure) may be particularly important. However, no studies have assessed cumulative CVH in YA and its association with target organ damage (TOD). Methods: CVH was defined using Life’s Essential 8 (LE8) score. CARDIA participants (ppts) with CVH assessed at ≥3 exams over 20 years of follow-up in YA (year [Y]0 to Y20 exams; mean ages 25 to 45 years) were included. Cumulative LE8 scores (cumLE8; higher = better CVH over time) were calculated as the sum of LE8 scores through YA carried forward between exams measured as point*years. Eight markers of TOD (listed in Results) were measured at subsequent exams (Y20 or Y25) including cardiac, renal, pulmonary, and neurologic markers. Associations of cumLE8 with markers of TOD were assessed using partial effects regression models adjusted for race, sex, and maximal education. Results: There were 3,485 ppts (43.4% men, 46.2% Black) with mean cumLE8 score of 1,448.6 (SD 211.4) point*years. Higher cumLE8 in YA was linearly associated with lower measures of cardiac (left ventricular mass index, carotid intima media thickness, prevalence of coronary artery calcium), renal (estimated glomerular filtration rate [eGFR] in men), and neurologic damage (proportion of white matter hyperintensity on brain MRI) ( Figure ). Higher cumLE8 was also linearly associated with better lung function (forced expiratory volume in 1 second, forced vital capacity). Urine albumin-creatinine ratio (in men and women) and eGFR (in women) were non-linearly associated with cumLE8. Conclusions: Our findings underscore the importance of high cumLE8 in YA and its association with reduced onset of TOD later in life. Primordial prevention strategies are needed to achieve and maintain high CVH through the critical period of YA.

Abstract 4138417: A Novel Echocardiography Risk Score Predicted Mortality In Patients With Heart Failure With Preserved Ejection Fraction.

Introduction: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit several echocardiographic abnormalities, including diastolic dysfunction, left ventricular (LV) hypertrophy, left atrial enlargement or pulmonary hypertrophy. It is not fully understood how these abnormalities are related with prognosis in HFpEF patients. Hypothesis: A combination of echocardiography parameters can predict clinical outcome in patients with HFpEF. Aims: This study aimed to develop a model to predict all-cause mortality in patients with HFpEF using echocardiography parameters. Methods: We analyzed data from 952 patients (81±9 years, 43% male) registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, a multicenter registry of patients hospitalized for acute decompensated HFpEF. Comprehensive echocardiography was performed before discharge. Patients were randomly assigned to the derivation and validation cohorts (2:1 ratio). Stepwise model selection was performed on age, sex and 26 echocardiography parameters to identify independent predictors of mortality. These predictors were used to construct a risk model for mortality. The accuracy of the risk score was validated using time-dependent ROC curves in both the derivation cohort (n=629) and in the validation cohort (n=323). Results: During the follow-up period (720 days, IQR: 376, 1100 days), all-cause death was observed in 248 patients (26.1%). Age, sex, diastolic (DWS), E/e’ ratio, LV mass index, LV posterior wall thickness (PWth), relative wall thickness (RWT), tricuspid regurgitant pressure gradient (TRPG) were selected as independent predictors of all-cause death. The score shown in the Table was applied to each factor, and the sum of the scores was calculated as the risk score. The AUC of the risk score for predicting 1-year mortality in the derivation cohort was 0.71 and the optimal cut-off value of 4.5 provided a sensitivity and specificity of 62.8% and 69.1%, respectively. The AUC for 1-year mortality in the validation cohort was 0.67. Conclusions: The novel echocardiography score effectively predicted mortality in HFpEF. This model could be a valuable tool for risk stratification.

Abstract 4118425: Prevalence and Spectrum of Pathogenic Genetic Variants in Korean Cardiomyopathy Patients: Insights from Next-Generation Sequencing

Background and Aim: Next-generation sequencing (NGS) is increasingly used to identify genetic variants associated with cardiomyopathies, which can aid in precise diagnosis and management. This study aimed to elucidate the prevalence and spectrum of pathogenic and likely pathogenic genetic variants in a cohort of Korean population diagnosed with different forms of cardiomyopathy. Methods: This retrospective study analyzed 122 patients diagnosed with cardiomyopathy at three tertiary hospitals in Korea, all of whom underwent NGS to identify genetic variants between December 2017 and October 2023. Detailed patient records, including clinical diagnoses, imaging results, and family histories, were reviewed to correlate genetic findings with phenotypic data. Results: Of the patients, 35 (28.7%) were found to have pathogenic or likely pathogenic variants, and 43 (35.2%) were found to have only variants of uncertain significance. Of the patients with pathogenic or likely pathogenic variants, 16 had hypertrophic cardiomyopathy (HCM) and 16 had dilated cardiomyopathy (DCM), while 3 remained with an uncertain clinical phenotype. In the HCM group, 16 patients exhibited variants predominantly in MYBPC3 (62.5%), followed by MYH7 (12.5%), and others such as TPM1, TNNI3, PRKAG2, and SCN5A (each 6.3%). Additionally, 43.8% of the HCM group had a familial history of sudden cardiac death or cardiomyopathy, with a mean left ventricular mass index (LVMi) of 148.3 ± 70.4 g/m2 and a mean maximal wall thickness of 17.7 ± 3.9 mm. The DCM group showed a different pattern, with TTN variants in 43.8%, LMNA in 18.8%, and others including MYBPC3, RBM20, TTN2, and KCNQ1 (each 6.3%). This group had a mean left ventricular ejection fraction (LVEF) of 27% and a LVMi of 119.7 g/m2. Conclusion: Our findings highlight significant genetic diversity in cardiomyopathies among Korean patients, with distinct genetic backgrounds observed in HCM and DCM. The high prevalence of specific mutations such as MYBPC3 in HCM and TTN in DCM could guide targeted genetic testing and personalized treatment strategies in these populations.

Abstract 4135617: Large Scale Proteomics Identifies Circulating Biomarkers Relating Atrial Fibrillation to Heart Failure: the Atherosclerosis Risk in Communities Study

Introduction: There is a bidirectional relationship between atrial fibrillation (AF) and heart failure (HF) risk. Data regarding shared and unique pathways underlying each are limited. Aims: Identify plasma proteins associated with both incident AF and HF and determine the extent to which associations with one outcome are conditional on interval occurrence of the other outcome. Methods: Among participants in the community-based Atherosclerosis Risk in Communities study free of HF and AF at study visit 5 (2011-2013), we measured 4,955 plasma proteins (SomaScan aptamer-affinity assay). We performed parallel analyses of individual protein associations with incident HF and AF using multivariable Cox regression adjusted for demographic and clinical covariates at Bonferroni significance. We then repeated the analysis for each outcome in models censoring participants with interval occurrence of the other outcome (i.e. incident AF censoring for interval HF, and vice versa). We tested associations of AF-related proteins with echocardiographic and Zio patch measures at Visit 5. Results: Among 4,118 participants included, mean age was 75±5 years, 60% were female, and 18% reported Black race. We identified 83 proteins associated with incident HF (n=355 incident events at 7 [IQR 6-8] year follow-up) and 24 with incident AF (n=517 incident events at 8 [7-9] years), of which 10 were associated with both. In models of incident HF censoring for interval AF, 63 (76%) proteins remained significantly associated with HF. In contrast, in the analysis of incident AF censoring for interval HF, only 4 (17%) proteins remained associated with AF, of which 3 were also associated with HF risk (Figure). These 4 AF-related proteins were associated with measures of LV diastolic function (LA volume, E/e’. average), LV mass index, LA function (LA reservoir, LA contraction), and supraventricular ectopy density (all p&lt;0.05). Conclusion: Nearly half of proteins reflecting AF risk also associate with HF, greater than 80% of AF-associated proteins are HF-dependent, and even those that are not correlate with measures of LV remodeling and dysfunction. These findings suggest that AF-related mechanisms among older adults are part of a wider HF syndrome.

Abstract 4139188: Myocardial perfusion, oxidative metabolism and fibrosis in heart failure with preserved ejection fraction

Background: Cardiac remodeling among individuals with heart failure with preserved ejection fraction (HFpEF) and its risk factors is incompletely understood. Non-invasive cardiac imaging can reliably assess myocardial oxidative metabolism, perfusion, fibrosis, systolic and diastolic function. Nevertheless, the interrelationships between these, particularly with oxidative metabolism, remain unresolved from health to HFpEF as most human studies lack complementary multi-modality imaging. Methods: We performed a cross-sectional study using multi-modality cardiovascular imaging in healthy individuals (n=17), those with hypertension (n=15), and patients with HFpEF (n=8). We quantified myocardial oxidative metabolism (K mono ) with 11 C-acetate positron emission tomography (PET), coronary flow reserve (CFR) with 13 N-ammonia PET, fibrosis (extracellular volume [ECV], LVEF and mass with magnetic resonance imaging (MRI), and LV diastolic filling pressure (E/e’) by echocardiography. The associations between myocardial oxidative metabolism, perfusion, and fibrosis across clinical status (health, hypertension, and HFpEF) were examined in multivariable models. Results: From health to HFpEF, we found significant graded declines in oxidative metabolism indexed to workload (K mono /RPP) (β = -1.66 x 10 -6 [95%CI: -3.12 x 10 -6 to -2.10 x 10 -6 ]; p = 0.027) and CFR (β = -0.76 [95% CI: -1.36 to -0.16]; p = 0.021), along with increased fibrosis (ECV) (β = 2.12% [95% CI: 0.10 to 4.14%]; p = 0.041), independent of LVEF, LV mass, E/e’, age, sex, and body mass index. The decline in oxidative metabolism from health to HFpEF was also independent of ECV and CFR (β = -2.98 x 10 -6 [95% CI: -5.62 x 10 -6 to -3.41 x 10 -6 ], p = 0.015). In contrast, the decline in CFR from health to HFpEF was no longer significant (p = 0.30) with further adjustment for ECV. Conclusions: HFpEF and its development involves progressive declines in myocardial oxidative metabolism and perfusion reserve with increase in fibrosis. The decline in myocardial oxidative metabolism from health to HFpEF is independent of fibrosis and perfusion reserve, suggesting oxidative metabolism may be a target for the prevention and treatment of HFpEF.

Abstract 4121812: Longitudinal Trajectory-Based Classification of Heart Failure with preserved Ejection Fraction: A Machine Learning Approach

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome characterized by heterogeneous pathophysiology and dynamic changes in cardiac structure and function. Current research predominantly focuses on left ventricular ejection fraction (LVEF) or left ventricular structures with predefined categories. This study hypothesized that applying unsupervised methodologies to longitudinal echocardiography will reveal distinct trajectory patterns in cardiac structure and function related to clinical outcomes in HFpEF patients. Methods: This retrospective cohort study, conducted at UC Davis Medical Center (2014 to 2022), consisted of adult patients with HFpEF. The inclusion criteria included ICD HF codes, a left ventricular ejection fraction (LVEF) ≥50%, and a Brain natriuretic peptide (BNP) ≥100 pg/ml or N-terminal-pro BNP (NT-proBNP) ≥225 pg/ml. Longitudinal data were analyzed using unsupervised machine learning, including UMAP for dimensionality reduction and Gaussian Mixture Models for clustering. Primary and secondary outcomes included all-cause mortality and changes in BNP levels, respectively. Results: The study included 1,626 patients. The cohort had a median age of 69 years, was 57.5% female, and 51.8% white. Three distinct echocardiographic trajectory patterns emerged (p&lt;.05) among the HFpEF cohort. Trajectory #1 (n=568) exhibited a high-stable pattern with the highest mortality rates, Trajectory #2 (n=512) showed a high-decreasing pattern with high mortality rates, and Trajectory #3 (n=546) had a low-increasing pattern with the lowest mortality rates. Trajectories varied significantly in baseline characteristics and longitudinal echocardiographic changes, with Trajectory #3 having a lower baseline left ventricular mass index (p&lt;.001) and a higher mean arterial pressure ( p =.001) compared to the other trajectories. Kaplan-Meier survival analysis indicated significant differences in survival among the trajectories ( p =.004). Conclusion: The study utilized unsupervised analysis of longitudinal echocardiographic data to identify three distinct HFpEF trajectories, each associated with unique clinical features and outcomes. These findings underscore the heterogeneity of HFpEF and highlight the potential trajectory-based patient stratification to improve targeted intervention strategies. Future validation in larger, multicenter cohorts is warranted to enhance HFpEF management and patient prognosis.

Abstract 4125300: Prognostic Value of NT-proBNP and the H 2 FPEF Score on Empagliflozin-associated Left Ventricular Remodeling: Insights from the EMPA-HEART and EMPA-HEART 2 CardioLink Trial

Background: NT-proBNP is a prognostic and diagnostic marker for heart failure while the H 2 FPEF score is used to aid in diagnosing heart failure with preserved ejection fraction. Aims: These post hoc analyses of the randomized controlled EMPA-HEART CardioLink-6 and EMPA-HEART 2 CardioLink-7 trials examined how baseline NT-proBNP and the H 2 FPEF score influenced empagliflozin-associated left ventricular (LV) remodeling in people with either type 2 diabetes and coronary artery disease or without diabetes but with cardiovascular risk factors. Methods: A total of 242 participants were assigned to either empagliflozin 10 mg QD (n=118) or placebo (n=124) for 6 months. NT-proBNP was measured and cardiac MRI performed at baseline and end-of-study. Two independent analyses were performed. One divided the participants into those with baseline NT-proBNP &lt; and ≧125 pg/mL and the other into those with H 2 FPEF score ≦2 and ≧3. The relationships between empagliflozin-associated LV mass and functional changes with baseline NT-proBNP and H 2 FPEF scores were assessed with linear models that adjusted for baseline differences (ANCOVA). Results: Mean age of the pooled cohort was 60.6 years; 14.0% were females, 37.2% had type 2 diabetes. Mean (SD) LV ejection fraction (LVEF) was 58.0 (10.2) %; median (IQR) NT-proBNP 77.5 (33, 164) pg/mL; mean (SD) H 2 FPEF score 2.9 (1.4). Empagliflozin (vs placebo) did not significantly alter LV mass index (mean [SD] -1.35 g/m 2 [0.75]; P=0.07) and LV end-systolic volume index (LVESVi; mean [SD] -1.37 mL/m 2 [0.74]; P=0.07) but did improve LVEF (mean [SD] 2.08% [0.82]; P=0.01). The effect of empagliflozin based on the subgroups of baseline NT-proBNP and H 2 FPEF scores are shown in Figures 1 and 2, respectively. Conclusions: These post hoc analyses suggest that lower baseline NT-proBNP levels and H 2 FPEF scores may be associated with more favourable reverse LV remodelling by empagliflozin and should be validated in larger studies.

Abstract 4126628: Worse Cardiac Structure and Function is Associated with Decline in Multiple Domains of Cognitive Function: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Cognitive impairment is cross-sectionally associated with worse cardiac structure/function. However, limited data exist regarding cardiac structure/function and longitudinal changes in cognitive function. Objective: Determine the association of cardiac structure and function with longitudinal changes in cognitive performance in late life. Methods: Among HF- and dementia-free participants in the community-based ARIC study who attended the 5th study visit (V5; 2011-2013), underwent protocol echocardiography, and completed a neurocognitive test battery at both V5 and study Visit 6 (V6; 2015-17), we assessed associations of cardiac structure and function measures with changes in both domain-specific and global cognitive scores between V5 and V6 using multivariable linear regression. Models were initially adjusted for demographics and education level, with additional models further adjusting for cardiovascular risk factors and disease at both V5 and V6. The neuropsychological test battery consisted of 10 neuropsychological tests that covered 3 domains of cognitive function: memory, executive functioning, and language. Factor scores were constructed for each cognitive domain, and their average represented a global composite score. Results: Among 2,988 included participants, mean age was 74±5 years, 60% were female, 20% reported Black race, and mean LVEF was 66±6%. Over a mean of 4.9±0.6 years (the V5 to V6 interval), raw scores declined for all neuropsychological tests. In fully adjusted models, worse diastolic function (larger LAVi) and LV remodeling (greater LV mass index) were associated with decline in executive function. Lower LVEF was associated with decline in language function, while worse LV longitudinal strain – a more sensitive measure of systolic dysfunction – was associated with decline in executive function, language function, and global cognition performance (all p&lt;0.05; Table). Conclusion: Subclinical LV remodeling and dysfunction is associated with greater declines in cognitive function over 5 years in late life. Differential associations were observed by cognitive domains, with executive function decline most uniformly associated with impairments in cardiac structure/function.

Abstract 4137204: Classifying Left Ventricular Hypertrophy from ECG in Overall Population and Bundle Branch Blocks: Machine Learning Models are Superior to Published ECG Criteria

Background: Published ECG criteria for left ventricular hypertrophy (LVH) have low diagnostic yield, esp. with right/left bundle branch block (RBBB/LBBB). Machine learning (ML) may improve LVH classification. Hypothesis: ML performs better than published LVH criteria to classify LVH from ECG in overall population, and subgroups of RBBB/LBBB. Methods: In addition to standard ECG features like rates, intervals, axis etc., R, S and overall QRS amplitudes, and voltage-time-integrals were extracted from standard 12 leads and reconstructed vectorcardiographic X, Y, Z lead representative beats. Further, a variational autoencoder was used to extract latent encodings from the representative beats. ML algorithms (logistic regression, random forest, light gradient boosted machine, multilayered perceptron, residual network, and convolutional neural network) were trained to predict LVH (LV mass index women &gt;95, men &gt;115 g/m 2 ) from ECG features on a training set of adult ECGs and echocardiogram within 45 days of each other (general population N=240,476, RBBB n=22,110, LBBB n=12,563). We obtained ROC AUCs in a separate validation set for LVH classification by (a) individual ECG variables, (b) published LVH criteria and (c) ML models. Results: As shown in Tables 1-2 and Figure 1 , for LVH classification among the validation sets, AUCs were highest for ML models, intermediate for univariable models and least for published criteria (best ML model vs. best criteria: general population women 0.77 vs. 0.63, men 0.78 vs. 0.63; RBBB women 0.70 vs. 0.57, men 0.77 vs. 0.57; LBBB women 0.71 vs. 0.55, men 0.72 vs. 0.54). Conclusions: ML models perform better than published LVH criteria at classifying LVH from ECG in overall population, RBBB and LBBB.

Effectiveness and safety of enzyme replacement therapy in the treatment of Fabry disease: a Chinese monocentric real-world study.

To assess the effectiveness and safety of enzyme replacement therapy (ERT) for treating Fabry disease in clinical practice. The clinical data of patients with Fabry disease were retrospectively collected and screened according to inclusion and exclusion criteria. The effectiveness of ERT was evaluated by analyzing the improvement in renal dysfunction (decreased estimated glomerular filtration rate (eGFR) and proteinuria), cardiac system injury (mainly increased left ventricular mass index (LVMI)), and neuropathic pain after ERT treatment. The safety of ERT was measured by summarizing the occurrence of adverse events (AE) and adverse drug reactions (ADR) before and after ERT. Sixteen patients with Fabry disease who underwent ERT treatment 2-36 times over a period of 2-89weeks were enrolled in the study. Among them, 13 received symptomatic treatment based on the involvement of various organs, 14 were treated with anti-inflammatory and anti-allergic drugs, and 16 had no AE or ADR. After ERT, there was no significant difference in (eGFR, microalbumin (mALB), 24h urinary protein quantitation (24h PRO), urinary albumin/creatinine ratio (ACR), uric acid (UA), and β2 microglobulin (β2MG) (P > 0.05), and the renal function remained stable or improved; ERT could significantly reduce left ventricular mass index (LVMI) (P = 0.043) and lactate dehydrogenase (LDH) (P = 0.031), and other cardiac function indexes had an improvement trend or remained stable, but the difference was not significant (P > 0.05). After ERT, the degree of limb pain in three of the four minor patients improved. ERT could effectively stabilize or improve renal and cardiac function and relieve neuropathic pain in patients with Fabry disease, and no AE occurred during treatment, and the clinical effectiveness and safety were satisfactory.